High and low responders to novelty: effects of adrenergic agents on the regulation of accumbal dopamine under challenged and non-challenged conditions.

The main goal of this study was to provide in vivo neurochemical evidence that mesolimbic alpha- and beta-adrenoceptors direct the release of mesolimbic dopamine. Both high responders to novelty and low responders to novelty were used to study the effects of intra-accumbal administered adrenergic agents on the dopamine release in the nucleus accumbens during two conditions, namely at rest (non-challenge) and when exposed to a "new cage" (challenge). Under non-challenged condition: phenylephrine (alpha-adrenergic agonist) induced a dose-dependent increase in dopamine release that was significantly larger in high responders; phentolamine (alpha-adrenoceptor antagonist) also induced a dose-dependent increase in dopamine that was significantly larger in low responders; isoproterenol (beta-adrenoceptor agonist) induced a dose-dependent increase in dopamine that did not differ between the two types of rat; propranolol (beta-adrenoceptor antagonist) did not change the dopamine release. Under challenged condition: phenylephrine and phentolamine both increased dopamine release without type-specific differences; only in low responders did isoproterenol increase the novelty-induced dopamine release; only in high responders did propranolol decrease the novelty-induced dopamine release. The in vivo neurochemical data are discussed in view of the outcome of earlier reported in vitro studies and pharmaco-behavioral studies. Overall the data reveal that mesolimbic noradrenaline has a dual role in the nucleus accumbens. It is argued that stimulation of alpha-adrenoceptors and beta-adrenoceptors, located postsynaptically on dopamine nerve-endings, inhibits and facilitates, respectively, dopamine release, whereas stimulation of presynaptic alpha-adrenoceptors inhibits the release of noradrenaline and, subsequently, disinhibits the release of dopamine. Moreover, it is argued that non-challenged high responders have a relatively low (alpha/beta) noradrenergic tonus that changes into a relatively high (alpha/beta) noradrenergic tonus during challenge, and that non-challenged low responders have a relatively high (alpha) adrenergic tonus that changes into a relatively low (alpha) noradrenergic tonus during challenge. In general, the present data clearly reveal that both alpha- and beta-adrenoceptors differentially regulate dopamine release in the nucleus accumbens. This regulation is individual-specific and depends on the test-condition (challenged versus non-challenged).